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Blood, 1 August 2008, Vol. 112, No. 3, pp. 619-625.
Prepublished online as a Blood First Edition Paper on May 20, 2008; DOI 10.1182/blood-2008-01-134833.
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IMMUNOBIOLOGY
Integrin  E(CD103)β7 influences cellular shape and motility in a ligand-dependent fashion
Stephanie Schlickum1,2,
Helga Sennefelder1,
Mike Friedrich1,
Gregory Harms1,
Martin J. Lohse1,3,
Peter Kilshaw4, and
Michael P. Schön1,2,5
1 Rudolf Virchow Center, Deutsche Forschungsgemeinschaft (DFG) Research Center for Experimental Biomedicine;
2 Department of Dermatology; and
3 Institute of Pharmacology and Toxicology, University of Würzburg, Würzburg, Germany;
4 The Babraham Institute, Cambridge, United Kingdom; and
5 Department of Dermatology and Venereology, University of Göttingen, Göttingen, Germany
While the extravasation cascade of lymphocytes is well characterized, data on their intraepithelial positioning and morphology are scant. However, the latter process is presumably crucial for many immune functions. Integrin  E(CD103)β7 has previously been implicated in epithelial retention of some T cells through binding to E-cadherin. Our current data suggest that E(CD103)β7 also determines shape and motility of some lymphocytes. Time-lapse microscopy showed that wild-type E(CD103)β7 conferred the ability to form cell protrusions/filopodia and to move in an amoeboid fashion on E-cadherin, an activity that was abrogated by E(CD103)β7-directed antibodies or cytochalasin D. The E-dependent motility was further increased (P < .001) when point-mutated E(CD103) locked in a constitutively active conformation was expressed. Moreover, different yellow fluorescent protein–coupled E(CD103) species demonstrated that the number and length of filopodia extended toward purified E-cadherin, cocultured keratinocytes, cryostat-cut skin sections, or epidermal sheets depended on functional E(CD103). The in vivo relevance of these findings was demonstrated by wild-type dendritic epidermal T cells (DETCs), which showed significantly more dendrites and spanned larger epidermal areas as compared with DETCs of E(CD103)-deficient mice (P < .001). Thus, integrin E(CD103)β7 is not only involved in epithelial retention, but also in shaping and proper intraepithelial morphogenesis of some leukocytes.
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